Platelets undergo the initial reactions which lead to hemostasis and to thrombosis. The nature of these reactions, i.e. the mechanisms whereby a specific stimulus interacts with a platelet membrane site, and those whereby the signal that a stimulation has occurred triggers an eventual platelet response are not yet fully elucidated. We seek to approach this problem by (a) isolating and characterizing the membrane binding site (i.e. receptor), utilizing photoreactive derivatives to obtain a covalently linked stimulus-receptor complex, (b) using the techniques for evaluation of changes in the platelet membrane potential and in intraplatelet pH which we have developed to probe this stimulus response, its transmembrane monovalent cation (Na+, K+, H+) gradient dependence, and its metabolic requirements, using specific indicators and/or specific antagonists, (c) evaluating the role of Ca++ in these responses to stimulation, utilizing arsenazo III, a sensitive Ca++ indicator, (d) determining the effect of certain membrane perturbants as well as some drugs on the platelet and on its response to thrombin stimulation. The results of these studies shold help us to understand the platelet reaction in response to stimuli, to delineate these mechanisms, and to design prevention or treatments for platelet related disorders of the circulatory system such as occur in thrombosis, atherosclerosis, thrombastenia, myelo-proliferative disorders and certain immune reactions.